@article {2023, title = {Conformational and mechanical stability of the isolated large subunit of membrane-bound [NiFe]-hydrogenase from Cupriavidus necator}, journal = {Frontiers in Microbiology}, volume = {13}, year = {2023}, abstract = {

Comprising at least a bipartite architecture, the large subunit of [NiFe]-hydrogenase harbors the catalytic nickel\–iron site while the small subunit houses an array of electron-transferring Fe-S clusters. Recently, some [NiFe]-hydrogenase large subunits have been isolated showing an intact and redox active catalytic cofactor. In this computational study we have investigated one of these metalloproteins, namely the large subunit HoxG of the membrane-bound hydrogenase from Cupriavidus necator (CnMBH), targeting its conformational and mechanical stability using molecular modelling and long all-atom Gaussian accelerated molecular dynamics (GaMD). Our simulations predict that isolated HoxG is stable in aqueous solution and preserves a large portion of its mechanical properties, but loses rigidity in regions around the active site, in contrast to the MBH heterodimer. Inspired by biochemical data showing dimerization of the HoxG protein and IR measurements revealing an increased stability of the [NiFe] cofactor in protein preparations with higher dimer content, corresponding simulations of homodimeric forms were also undertaken. While the monomeric subunit contains several flexible regions, our data predicts a regained rigidity in homodimer models. Furthermore, we computed the electrostatic properties of models obtained by enhanced sampling with GaMD, which displays a significant amount of positive charge at the protein surface, especially in solvent-exposed former dimer interfaces. These data offer novel insights on the way the [NiFe] core is protected from de-assembly and provide hints for enzyme anchoring to surfaces, which is essential information for further investigations on these minimal enzymes.

}, issn = {1664-302X}, doi = {10.3389/fmicb.2022.1073315}, url = {https://www.frontiersin.org/articles/10.3389/fmicb.2022.1073315}, author = {Dragelj, Jovan and Karafoulidi-Retsou, Chara and Katz, Sagie and Lenz, Oliver and Zebger, Ingo and Caserta, Giorgio and S Sacquin-Mora and Mroginski, Maria Andrea} } @article {2022|2150, title = {Modeling the Dynamics of Protein-Protein Interfaces, How and Why?}, journal = {Molecules}, volume = {27}, year = {2022}, pages = {1841}, abstract = {

Protein-protein assemblies act as a key component in numerous cellular processes. Their accurate modeling at the atomic level remains a challenge for structural biology. To address this challenge, several docking and a handful of deep learning methodologies focus on modeling protein-protein interfaces. Although the outcome of these methods has been assessed using static reference structures, more and more data point to the fact that the interaction stability and specificity is encoded in the dynamics of these interfaces. Therefore, this dynamics information must be taken into account when modeling and assessing protein interactions at the atomistic scale. Expanding on this, our review initially focuses on the recent computational strategies aiming at investigating protein-protein interfaces in a dynamic fashion using enhanced sampling, multi-scale modeling, and experimental data integration. Then, we discuss how interface dynamics report on the function of protein assemblies in globular complexes, in fuzzy complexes containing intrinsically disordered proteins, as well as in active complexes, where chemical reactions take place across the protein-protein interface.

}, issn = {1420-3049}, doi = {10.3390/molecules27061841}, url = {https://www.mdpi.com/1420-3049/27/6/1841}, author = {Karaca, Ezgi and Pr{\'e}vost, Chantal and S Sacquin-Mora} } @article {2022|2153, title = {Multiscale Computational Study of the Conformation of the Full-Length Intrinsically Disordered Protein MeCP2.}, journal = {J Chem Inf Model}, volume = {62}, year = {2022}, month = {2022 02 28}, pages = {958-970}, abstract = {

The malfunction of the methyl-CpG binding protein 2 (MeCP2) is associated with the Rett syndrome, one of the most common causes of cognitive impairment in females. MeCP2 is an intrinsically disordered protein (IDP), making its experimental characterization a challenge. There is currently no structure available for the full-length MeCP2 in any of the databases, and only the structure of its MBD domain has been solved. We used this structure to build a full-length model of MeCP2 by completing the rest of the protein via ab initio modeling. Using a combination of all-atom and coarse-grained simulations, we characterized its structure and dynamics as well as the conformational space sampled by the ID and transcriptional repression domain (TRD) domains in the absence of the rest of the protein. The present work is the first computational study of the full-length protein. Two main conformations were sampled in the coarse-grained simulations: a globular structure similar to the one observed in the all-atom force field and a two-globule conformation. Our all-atom model is in good agreement with the available experimental data, predicting amino acid W104 to be buried, amino acids R111 and R133 to be solvent-accessible, and having a 4.1\% α-helix content, compared to the 4\% found experimentally. Finally, we compared the model predicted by AlphaFold to our Modeller model. The model was not stable in water and underwent further folding. Together, these simulations provide a detailed (if perhaps incomplete) conformational ensemble of the full-length MeCP2, which is compatible with experimental data and can be the basis of further studies, e.g., on mutants of the protein or its interactions with its biological partners.

}, issn = {1549-960X}, doi = {10.1021/acs.jcim.1c01354}, author = {Ch{\'a}vez-Garc{\'\i}a, Cecilia and J{\'e}r{\^o}me H{\'e}nin and Karttunen, Mikko} } @article {2020|2142, title = {Scalable molecular dynamics on CPU and GPU architectures with NAMD}, journal = {The Journal of Chemical Physics}, volume = {153}, year = {2020}, chapter = {044130}, abstract = {

NAMD is a molecular dynamics program designed for high-performance simulations of very large biological objects on CPU- and GPU-based architectures. NAMD offers scalable performance on petascale parallel supercomputers consisting of hundreds of thousands of cores, as well as on inexpensive commodity clusters commonly found in academic environments. It is written in C++ and leans on Charm++ parallel objects for optimal performance on low-latency architectures. NAMD is a versatile, multipurpose code that gathers state-of-the-art algorithms to carry out simulations in apt thermodynamic ensembles, using the widely popular CHARMM, AMBER, OPLS, and GROMOS biomolecular force fields. Here, we review the main features of NAMD that allow both equilibrium and enhanced-sampling molecular dynamics simulations with numerical efficiency. We describe the underlying concepts utilized by NAMD and their implementation, most notably for handling long-range electrostatics; controlling the temperature, pressure, and pH; applying external potentials on tailored grids; leveraging massively parallel resources in multiple-copy simulations; and hybrid quantum-mechanical/molecular-mechanical descriptions. We detail the variety of options offered by NAMD for enhanced-sampling simulations aimed at determining free-energy differences of either alchemical or geometrical transformations and outline their applicability to specific problems. Last, we discuss the roadmap for the development of NAMD and our current efforts toward achieving optimal performance on GPU-based architectures, for pushing back the limitations that have prevented biologically realistic billion-atom objects to be fruitfully simulated, and for making large-scale simulations less expensive and easier to set up, run, and analyze. NAMD is distributed free of charge with its source code at www.ks.uiuc.edu.

}, keywords = {NAMD}, doi = {10.1063/5.0014475}, url = {https://aip.scitation.org/doi/10.1063/5.0014475}, author = {James Phillips and David Hardy and Julio Maia and John Stone and Joao Ribeiro and Rafael Bernardi and Ronak Buch and Giacomo Fiorin and J{\'e}r{\^o}me H{\'e}nin and Wei Jiang and Ryan McGreevy and Melo, Marcelo Cardoso dos Reis and Brian Radak and Robert Skeel and Abhishek Singharoy and Yi Wang and Benoit Roux and Aleksei Aksimentiev and Zan Luthey-Schulten and Laxmikant Kale and Klaus Schulten and Christophe Chipot and Emad Tajkhorshid} } @article {2020|2124, title = {Temperature Unmasks Allosteric Propensity in a Thermophilic Malate Dehydrogenase via Dewetting and Collapse}, journal = {The Journal of Physical Chemistry B}, volume = {124}, year = {2020}, pages = {1001-1008}, doi = {10.1021/acs.jpcb.9b10776}, url = {https://doi.org/10.1021/acs.jpcb.9b10776}, author = {Katava, M. and Marchi, M. and Madern, D. and Sztucki, M. and Maccarini, M. and Sterpone, F.} } @article {2019|2080, title = {Highlights from the Faraday Discussion on Artificial Water Channels, Glasgow, UK.}, journal = {Chem Commun (Camb)}, volume = {55}, year = {2019}, month = {2019 Apr 07}, pages = {3853-3858}, issn = {1364-548X}, doi = {10.1039/c9cc90112d}, author = {Barboiu, Mihail and Kumar, Manish and Marc Baaden and Gale, Philip A and Hinds, Bruce J} } @article {2019|2079, title = {Molecular Graphics: Bridging Structural Biologists and Computer Scientists.}, journal = {Structure}, volume = {27}, year = {2019}, month = {2019 11 05}, pages = {1617-1623}, abstract = {

Visualization of molecular structures is one of the most common tasks carried out by structural biologists, typically using software, such as Chimera, COOT, PyMOL, or VMD. In this Perspective article, we outline how past developments in computer graphics and data visualization have expanded the understanding of biomolecular function, and we summarize recent advances that promise to further transform structural biology. We also highlight how progress in molecular graphics has been impeded by communication barriers between two communities: the computer scientists driving these advances, and the structural and computational biologists who stand to benefit. By pointing to canonical papers and explaining technical progress underlying new graphical developments in simple terms, we aim to improve communication between these communities; this, in turn, would help shape future developments in molecular graphics.

}, issn = {1878-4186}, doi = {10.1016/j.str.2019.09.001}, author = {Martinez, Xavier and Krone, Michael and Alharbi, Naif and Rose, Alexander S and Laramee, Robert S and O{\textquoteright}Donoghue, Sean and Marc Baaden and Chavent, Matthieu} } @conference {2019|2099, title = {QuickSES: A Library for Fast Computation of Solvent Excluded Surfaces}, booktitle = {Workshop on Molecular Graphics and Visual Analysis of Molecular Data}, year = {2019}, publisher = {The Eurographics Association}, organization = {The Eurographics Association}, isbn = {978-3-03868-085-7}, doi = {10.2312/molva.20191095}, author = {Martinez, Xavier and Krone, Michael and Marc Baaden}, editor = {Byska, Jan and Krone, Michael and Sommer, Bj{\"o}rn} } @article {2019|2119, title = {Stability Effect of Quinary Interactions Reversed by Single Point Mutations}, journal = {Journal of the American Chemical Society}, volume = {141}, year = {2019}, pages = {4660-4669}, doi = {10.1021/jacs.8b13025}, url = {https://doi.org/10.1021/jacs.8b13025}, author = {Gnutt, David and Timr, Stepan and Ahlers, Jonas and K{\"o}nig, Benedikt and Manderfeld, Emily and Heyden, Matthias and Sterpone, Fabio and Ebbinghaus, Simon} } @inbook {2018|2085, title = {Applications to water transport systems: general discussion.}, booktitle = {Faraday Discuss}, volume = {209}, year = {2018}, month = {2018 09 28}, pages = {389-414}, issn = {1364-5498}, doi = {10.1039/c8fd90022a}, author = {Marc Baaden and Barboiu, Mihail and Borthakur, Manash Pratim and Chen, Chun-Long and Coalson, Rob and Davis, Jeffery and Freger, Viatcheslav and Gong, Bing and H{\'e}lix-Nielsen, Claus and Hickey, Robert and Hinds, Bruce and Hirunpinyopas, Wisit and Horner, Andreas and Hou, Jun-Li and Hummer, Gerhard and Iamprasertkun, Pawin and Kazushi, Kinbara and Kumar, Manish and Legrand, Yves-Marie and Lokesh, Mahesh and Mi, Baoxia and Mitra, Sushanta and Murail, Samuel and Noy, Aleksandr and Nunes, Suzana and Pohl, Peter and Song, Qilei and Song, Woochul and T{\"o}rnroth-Horsefield, Susanna and Vashisth, Harish} } @inbook {2018|2082, title = {Biomimetic water channels: general discussion.}, booktitle = {Faraday Discuss}, volume = {209}, year = {2018}, month = {2018 09 28}, pages = {205-229}, issn = {1364-5498}, doi = {10.1039/c8fd90020e}, author = {Marc Baaden and Barboiu, Mihail and Bill, Roslyn M and Chen, Chun-Long and Davis, Jeffery and Di Vincenzo, Maria and Freger, Viatcheslav and Fr{\"o}ba, Michael and Gale, Philip A and Gong, Bing and H{\'e}lix-Nielsen, Claus and Hickey, Robert and Hinds, Bruce and Hou, Jun-Li and Hummer, Gerhard and Kumar, Manish and Legrand, Yves-Marie and Lokesh, Mahesh and Mi, Baoxia and Murail, Samuel and Pohl, Peter and Sansom, Mark and Song, Qilei and Song, Woochul and T{\"o}rnroth-Horsefield, Susanna and Vashisth, Harish and V{\"o}gele, Martin} } @article {2018|2112, title = {Breaking down cellulose fibrils with a mid-infrared laser}, journal = {Cellulose}, volume = {25}, year = {2018}, pages = {5553{\textendash}5568}, author = {Domin, Dominik and Man, Viet Hoang and Van-Oanh, Nguyen-Thi and Wang, Junmei and Kawasaki, Takayasu and Philippe Derreumaux and Phuong Hoang Nguyen} } @article {2018|2088, title = {From Virtual Reality to Immersive Analytics in Bioinformatics.}, journal = {J Integr Bioinform}, volume = {15}, year = {2018}, month = {2018 Jul 09}, abstract = {

Bioinformatics-related research produces huge heterogeneous amounts of data. This wealth of information includes data describing metabolic mechanisms and pathways, proteomics, transcriptomics, and metabolomics. Often, the visualization and exploration of related structural - usually molecular - data plays an important role in the aforementioned contexts. For decades, virtual reality (VR)-related technologies were developed and applied to Bioinformatics problems. Often, these approaches provide \"just\" visual support of the analysis, e.g. in the case of exploring and interacting with a protein on a 3D monitor and compatible interaction hardware. Moreover, in the past these approaches were limited to cost-intensive professional visualization facilities. The advent of new affordable, and often mobile technologies, provides high potential for using similar approaches on a regular basis for daily research. Visual Analytics is successfully being used for several years to analyze complex and heterogeneous datasets. Immersive Analytics combines these approaches now with new immersive and interactive technologies. This publication provides a short overview of related technologies, their history and Bioinformatics-related approaches. Six new applications on the path from VR to Immersive Analytics are being introduced and discussed.

}, keywords = {Computer Graphics, Imaging, Three-Dimensional, Molecular Conformation, Proteins, Software, User-Computer Interface, Virtual Reality}, issn = {1613-4516}, doi = {10.1515/jib-2018-0043}, author = {Sommer, Bj{\"o}rn and Marc Baaden and Krone, Michael and Woods, Andrew} } @inbook {2018|2084, title = {The modelling and enhancement of water hydrodynamics: general discussion.}, booktitle = {Faraday Discuss}, volume = {209}, year = {2018}, month = {2018 09 28}, pages = {273-285}, issn = {1364-5498}, doi = {10.1039/c8fd90021c}, author = {Marc Baaden and Borthakur, Manash Pratim and Casanova, Serena and Coalson, Rob and Freger, Viatcheslav and Gonzalez, Miguel and G{\'o}ra, Artur and Hinds, Bruce and Hirunpinyopas, Wisit and Hummer, Gerhard and Kumar, Manish and Lynch, Charlotte and Murail, Samuel and Noy, Aleksandr and Sansom, Mark and Song, Qilei and Vashisth, Harish and V{\"o}gele, Martin} } @article {2018|2092, title = {Oriented chiral water wires in artificial transmembrane channels.}, journal = {Sci Adv}, volume = {4}, year = {2018}, month = {2018 03}, pages = {eaao5603}, abstract = {

Aquaporins (AQPs) feature highly selective water transport through cell membranes, where the dipolar orientation of structured water wires spanning the AQP pore is of considerable importance for the selective translocation of water over ions. We recently discovered that water permeability through artificial water channels formed by stacked imidazole I-quartet superstructures increases when the channel water molecules are highly organized. Correlating water structure with molecular transport is essential for understanding the underlying mechanisms of (fast) water translocation and channel selectivity. Chirality adds another factor enabling unique dipolar oriented water structures. We show that water molecules exhibit a dipolar oriented wire structure within chiral I-quartet water channels both in the solid state and embedded in supported lipid bilayer membranes (SLBs). X-ray single-crystal structures show that crystallographic water wires exhibit dipolar orientation, which is unique for chiral I-quartets. The integration of I-quartets into SLBs was monitored with a quartz crystal microbalance with dissipation, quantizing the amount of channel water molecules. Nonlinear sum-frequency generation vibrational spectroscopy demonstrates the first experimental observation of dipolar oriented water structures within artificial water channels inserted in bilayer membranes. Confirmation of the ordered confined water is obtained via molecular simulations, which provide quantitative measures of hydrogen bond strength, connectivity, and the stability of their dipolar alignment in a membrane environment. Together, uncovering the interplay between the dipolar aligned water structure and water transport through the self-assembled I-quartets is critical to understanding the behavior of natural membrane channels and will accelerate the systematic discovery for developing artificial water channels for water desalting.

}, issn = {2375-2548}, doi = {10.1126/sciadv.aao5603}, author = {Kocsis, Istvan and Sorci, Mirco and Vanselous, Heather and Murail, Samuel and Sanders, Stephanie E and Licsandru, Erol and Legrand, Yves-Marie and van der Lee, Arie and Marc Baaden and Petersen, Poul B and Belfort, Georges and Barboiu, Mihail} } @article {2018, title = {RecA requires two molecules of Mg2+ ions for its optimal strand exchange activity in vitro}, journal = {Nucleic Acids Res}, volume = {ahead of print}, year = {2018}, month = {Jan}, abstract = {

Mg2+ ion stimulates the DNA strand exchange reaction catalyzed by RecA, a key step in homologous recombination. To elucidate the molecular mechanisms underlying the role of Mg2+ and the strand exchange reaction itself, we investigated the interaction of RecA with Mg2+ and sought to determine which step of the reaction is affected. Thermal stability, intrinsic fluorescence, and native mass spectrometric analyses of RecA revealed that RecA binds at least two Mg2+ ions with KD \‚{\^a}{\`a} 2 mM and 5 mM. Deletion of the C-terminal acidic tail of RecA made its thermal stability and fluorescence characteristics insensitive to Mg2+ and similar to those of full-length RecA in the presence of saturating Mg2+. These observations, together with the results of a molecular dynamics simulation, support the idea that the acidic tail hampers the strand exchange reaction by interacting with other parts of RecA, and that binding of Mg2+ to the tail prevents these interactions and releases RecA from inhibition. We observed that binding of the first Mg2+ stimulated joint molecule formation, whereas binding of the second stimulated progression of the reaction. Thus, RecA is actively involved in the strand exchange step as well as bringing the two DNAs close to each other.

}, doi = {10.1093/nar/gky048}, author = {Kim, Raeyeong and Kanamaru, Shuji and Mikawa, Tsutomu and Chantal Pr{\'e}vost and Ishii, Kentaro and Ito, Kentaro and Uchiyama, Susumu and Oda, Masayuki and Iwasaki, Hiroshi and Kim, Seog K and Takahashi, Masayuki} } @inbook {2018|2083, title = {Structure and function of natural proteins for water transport: general discussion.}, booktitle = {Faraday Discuss}, volume = {209}, year = {2018}, month = {2018 09 28}, pages = {83-95}, keywords = {Molecular Structure, Proteins, Water}, issn = {1364-5498}, doi = {10.1039/c8fd90019a}, author = {Marc Baaden and Barboiu, Mihail and Bill, Roslyn M and Casanova, Serena and Chen, Chun-Long and Conner, Matthew and Freger, Viatcheslav and Gong, Bing and G{\'o}ra, Artur and Hinds, Bruce and Horner, Andreas and Hummer, Gerhard and Kumar, Manish and Lokesh, Mahesh and Mitra, Sushanta and Noy, Aleksandr and Pohl, Peter and Sadet, Aude and Sansom, Mark and T{\"o}rnroth-Horsefield, Susanna and Vashisth, Harish} } @article {2017|2033, title = {Configurational Disorder of Water Hydrogen Bond Network at the Protein Dynamical Transition}, volume = {121}, year = {2017}, pages = {6792-6798}, author = {O. Rahaman and M. Kalimeri and M. Katava and A. Paciaroni and F. Sterpone} } @article {2017|2025, title = {Critical structural fluctuations of proteins upon thermal unfolding challenge the Lindemann criterion}, journal = {Proc Natl Acad Sci U S A}, volume = {114}, year = {2017}, month = {Aug}, pages = {9361-9366}, abstract = {

Internal subnanosecond timescale motions are key for the function of proteins, and are coupled to the surrounding solvent environment. These fast fluctuations guide protein conformational changes, yet their role for protein stability, and for unfolding, remains elusive. Here, in analogy with the Lindemann criterion for the melting of solids, we demonstrate a common scaling of structural fluctuations of lysozyme protein embedded in different environments as the thermal unfolding transition is approached. By combining elastic incoherent neutron scattering and advanced molecular simulations, we show that, although different solvents modify the protein melting temperature, a unique dynamical regime is attained in proximity of thermal unfolding in all solvents that we tested. This solvation shell-independent dynamical regime arises from an equivalent sampling of the energy landscape at the respective melting temperatures. Thus, we propose that a threshold for the conformational entropy provided by structural fluctuations of proteins exists, beyond which thermal unfolding is triggered.

}, keywords = {cell thermal stability, Lindemann criterion, Molecular Dynamics Simulation, neutron scattering, protein dynamics}, doi = {10.1073/pnas.1707357114}, author = {Katava, Marina and Guillaume Stirnemann and Zanatta, Marco and Capaccioli, Simone and Pachetti, Maria and Ngai, K L and Sterpone, Fabio and Paciaroni, Alessandro} } @conference {2017|2101, title = {Molecular Visualization of Computational Biology Data: A Survey of Surveys}, booktitle = {EuroVis 2017 - Short Papers}, year = {2017}, publisher = {The Eurographics Association}, organization = {The Eurographics Association}, isbn = {978-3-03868-043-7}, doi = {10.2312/eurovisshort.20171146}, author = {Alharbi, Naif and Alharbi, Mohammad and Martinez, Xavier and Krone, Michael and Rose, Alexander S. and Marc Baaden and Laramee, Robert S. and Chavent, Matthieu}, editor = {Barbora Kozlikova and Tobias Schreck and Thomas Wischgoll} } @article {2017|2102, title = {Visualization of Biomolecular Structures: State of the Art Revisited: Visualization of Biomolecular Structures}, journal = {Computer Graphics Forum}, volume = {36}, year = {2017}, pages = {178{\textendash}204}, issn = {01677055}, doi = {10.1111/cgf.13072}, url = {http://doi.wiley.com/10.1111/cgf.13072}, author = {Kozlikova, B. and Krone, M. and Falk, M. and Lindow, N. and Marc Baaden and Baum, D. and Viola, I. and Parulek, J. and Hege, H.-C.} } @article {2016|1630, title = {Evaluation of the coarse-grained OPEP force field for protein-protein docking}, journal = {Bmc Biophysics}, volume = {9}, year = {2016}, month = {apr}, abstract = {Background: Knowing the binding site of protein-protein complexes helps understand their function and shows possible regulation sites. The ultimate goal of protein-protein docking is the prediction of the three-dimensional structure of a protein-protein complex. Docking itself only produces plausible candidate structures, which must be ranked using scoring functions to identify the structures that are most likely to occur in nature. Methods: In this work, we rescore rigid body protein-protein predictions using the optimized potential for efficient structure prediction (OPEP), which is a coarse-grained force field. Using a force field based on continuous functions rather than a grid-based scoring function allows the introduction of protein flexibility during the docking procedure. First, we produce protein-protein predictions using ZDOCK, and after energy minimization via OPEP we rank them using an OPEP-based soft rescoring function. We also train the rescoring function for different complex classes and demonstrate its improved performance for an independent dataset. Results: The trained rescoring function produces a better ranking than ZDOCK for more than 50 \% of targets, rising to over 70 \% when considering only enzyme/inhibitor complexes. Conclusions: This study demonstrates for the first time that energy functions derived from the coarse-grained OPEP force field can be employed to rescore predictions for protein-protein complexes.}, issn = {2046-1682}, doi = {10.1186/s13628-016-0029-y}, author = {Kynast, Philipp and Philippe Derreumaux and Strodel, Birgit} } @article {2016|1447, title = {{S}alt-{E}xcluding {A}rtificial {W}ater {C}hannels {E}xhibiting {E}nhanced {D}ipolar {W}ater and {P}roton {T}ranslocation}, journal = {J. Am. Chem. Soc.}, volume = {138}, number = {16}, year = {2016}, month = {apr}, pages = {5403{\textendash}5409}, author = {Licsandru, E. and Kocsis, I. and Shen, Y. X. and Murail, S. and Legrand, Y. M. and van der Lee, A. and Tsai, D. and Marc Baaden and Kumar, M. and Barboiu, M.} } @article {2016|1687, title = {Stability and Function at High Temperature. What Makes a Thermophilic GTPase Different from Its Mesophilic Homologue}, journal = {J. Phys. Chem. B}, volume = {120}, year = {2016}, pages = {2721{\textendash}2730}, abstract = {

Comparing homologous enzymes adapted to different thermal environments aids to shed light on their delicate stability/function trade-off. Protein mechanical rigidity was postulated to secure stability and high-temperature functionality of thermophilic proteins. In this work, we challenge the corresponding-state principle for a pair of homologous GTPase domains by performing extensive molecular dynamics simulations, applying conformational and kinetic clustering, as well as exploiting an enhanced sampling technique (REST2). While it was formerly shown that enhanced protein flexibility and high temperature stability can coexist in the apo hyperthermophilic variant, here we focus on the holo states of both homologues by mimicking the enzymatic turnover. We clearly show that the presence of the ligands affects the conformational landscape visited by the proteins, and that the corresponding state principle applies for some functional modes. Namely, in the hyperthermophilic species, the flexibility of the effec...

}, issn = {15205207}, doi = {10.1021/acs.jpcb.6b00306}, author = {Katava, Marina and Kalimeri, Maria and Guillaume Stirnemann and Fabio Sterpone} } @article {2016|1764, title = {Thermal activation of {\textquoteleft}allosteric-like{\textquoteright} large-scale motions in a eukaryotic Lactate Dehydrogenase.}, journal = {Sci. Reports}, volume = {7}, year = {2016}, pages = {41092}, author = {M. Katava and M. Maccarini and G. Villain and A. Paciaroni and M. Sztucki and O. Ivanova and D. Madern and Fabio Sterpone} } @article {2016, title = {Visual Analysis of Biomolecular Cavities: State of the Art}, journal = {Comput. Graphics Forum}, volume = {35}, number = {3}, year = {2016}, month = {jun}, pages = {527{\textendash}551}, keywords = {AMBIENT OCCLUSION, ANALYTICAL SHAPE, BINDING-SITE IDENTIFICATION, LIGAND-BINDING, PORE DIMENSIONS, PROTEIN CAVITIES, SURFACE, TIME MOLECULAR VISUALIZATION, TRAVEL DEPTH, WEB SERVER}, url = {https://hal.archives-ouvertes.fr/hal-01400464}, author = {Krone, M. and Kozlikova, B. and Lindow, N. and Marc Baaden and Baum, D. and Parulek, J. and Hege, H.-C. and Viola, I.} } @article {2016|1401, title = {Visualization of Biomolecular Structures: State of the Art Revisited}, journal = {Comput. Graphics Forum}, year = {2016}, month = {nov}, url = {https://hal.archives-ouvertes.fr/hal-01400465}, author = {Kozlikova, B. and Krone, M. and Falk, M. and Lindow, N. and Marc Baaden and Baum, D. and Viola, I. and Parulek, J. and Hege, H.-C.} } @article {2015|1910, title = {Are coarse-grained models apt to detect protein thermal stability? The case of \{OPEP\} force field}, journal = {J. Non-cryst. Solids}, volume = {407}, year = {2015}, note = {7th IDMRCS: Relaxation in Complex Systems}, pages = {494{\textendash}501}, keywords = {Conformational substates network}, doi = {10.1016/j.jnoncrysol.2014.07.005}, url = {http://www.sciencedirect.com/science/article/pii/S0022309314002889}, author = {Maria Kalimeri and Philippe Derreumaux and Fabio Sterpone} } @article {2015|1664, title = {Membrane Protein Structure, Function, and Dynamics: a Perspective from Experiments and Theory.}, journal = {J. Membr. Biol.}, volume = {248}, year = {2015}, publisher = {Biomedical Research Foundation, Academy of Athens, 4 Soranou Ephessiou, 11527, Athens, Greece, zcournia@bioacademy.gr.}, chapter = {611}, abstract = {

Membrane proteins mediate processes that are fundamental for the flourishing of biological cells. Membrane-embedded transporters move ions and larger solutes across membranes; receptors mediate communication between the cell and its environment and membrane-embedded enzymes catalyze chemical reactions. Understanding these mechanisms of action requires knowledge of how the proteins couple to their fluid, hydrated lipid membrane environment. We present here current studies in computational and experimental membrane protein biophysics, and show how they address outstanding challenges in understanding the complex environmental effects on the structure, function, and dynamics of membrane proteins.

}, doi = {10.1007/s00232-015-9802-0}, author = {Cournia, Zoe and Allen, Toby W. and Andricioaei, Ioan and Antonny, Bruno and Baum, Daniel and Grace Brannigan and Buchete, Nicolae-Viorel and Deckman, Jason T. and Delemotte, Lucie and Del Val, Coral and Friedman, Ran and Gkeka, Paraskevi and Hege, Hans-Christian and J{\'e}r{\^o}me H{\'e}nin and Kasimova, Marina A. and Kolocouris, Antonios and Michael L Klein and Khalid, Syma and Lemieux, M Joanne and Lindow, Norbert and Roy, Mahua and Selent, Jana and Mounir Tarek and Tofoleanu, Florentina and Vanni, Stefano and Urban, Sinisa and Wales, David J. and Smith, Jeremy C. and Bondar, Ana-Nicoleta} } @article {2015|1732, title = {The poor homology stringency in the heteroduplex allows strand exchange to incorporate desirable mismatches without sacrificing recognition in vivo}, journal = {Nucleic Acids Res.}, volume = {43}, year = {2015}, month = {jul}, pages = {6473{\textendash}85}, abstract = {

RecA family proteins are responsible for homology search and strand exchange. In bacteria, homology search begins after RecA binds an initiating single-stranded DNA (ssDNA) in the primary DNA-binding site, forming the presynaptic filament. Once the filament is formed, it interrogates double-stranded DNA (dsDNA). During the interrogation, bases in the dsDNA attempt to form Watson-Crick bonds with the corresponding bases in the initiating strand. Mismatch dependent instability in the base pairing in the heteroduplex strand exchange product could provide stringent recognition; however, we present experimental and theoretical results suggesting that the heteroduplex stability is insensitive to mismatches. We also present data suggesting that an initial homology test of 8 contiguous bases rejects most interactions containing more than 1/8 mismatches without forming a detectable 20 bp product. We propose that, in vivo, the sparsity of accidental sequence matches allows an initial 8 bp test to rapidly reject almost all non-homologous sequences. We speculate that once the initial test is passed, the mismatch insensitive binding in the heteroduplex allows short mismatched regions to be incorporated in otherwise homologous strand exchange products even though sequences with less homology are eventually rejected.

}, doi = {10.1093/nar/gkv610}, author = {Danilowicz, Claudia and Yang, Darren and Kelley, Craig and Chantal Pr{\'e}vost and Prentiss, Mara} } @article {2015|1668, title = {Role of Internal Water on Protein Thermal Stability: The Case of Homologous G Domains.}, journal = {J. Phys. Chem. B}, volume = {119}, year = {2015}, month = {jul}, pages = {8939{\textendash}49}, abstract = {

In this work, we address the question of whether the enhanced stability of thermophilic proteins has a direct connection with internal hydration. Our model systems are two homologous G domains of different stability: the mesophilic G domain of the elongation factor thermal unstable protein from E. coli and the hyperthermophilic G domain of the EF-1α protein from S. solfataricus. Using molecular dynamics simulation at the microsecond time scale, we show that both proteins host water molecules in internal cavities and that these molecules exchange with the external solution in the nanosecond time scale. The hydration free energy of these sites evaluated via extensive calculations is found to be favorable for both systems, with the hyperthermophilic protein offering a slightly more favorable environment to host water molecules. We estimate that, under ambient conditions, the free energy gain due to internal hydration is about 1.3 kcal/mol in favor of the hyperthermophilic variant. However, we also find that, at the high working temperature of the hyperthermophile, the cavities are rather dehydrated, meaning that under extreme conditions other molecular factors secure the stability of the protein. Interestingly, we detect a clear correlation between the hydration of internal cavities and the protein conformational landscape. The emerging picture is that internal hydration is an effective observable to probe the conformational landscape of proteins. In the specific context of our investigation, the analysis confirms that the hyperthermophilic G domain is characterized by multiple states and it has a more flexible structure than its mesophilic homologue.

}, issn = {1520-5207}, doi = {10.1021/jp507571u}, author = {Rahaman, Obaidur and Kalimeri, Maria and Melchionna, Simone and J{\'e}r{\^o}me H{\'e}nin and Fabio Sterpone} } @conference {2015|1408, title = {Visualization of Biomolecular Structures: State of the Art}, booktitle = {Eurographics Conference on Visualization (EuroVis) - STARs}, year = {2015}, publisher = {The Eurographics Association}, organization = {The Eurographics Association}, author = {Kozlikova, Barbora and Krone, Michael and Lindow, Norbert and Falk, Martin and Marc Baaden and Baum, Daniel and Viola, Ivan and Parulek, Julius and Hege, Hans-Christian}, editor = {R. Borgo and F. Ganovelli and I. Viola} } @article {2014|1669, title = {CHARMM36 united atom chain model for lipids and surfactants.}, journal = {J. Phys. Chem. B}, volume = {118}, number = {2}, year = {2014}, month = {jan}, pages = {547{\textendash}556}, publisher = {, Maryland 20742, United States.}, abstract = {Molecular simulations of lipids and surfactants require accurate parameters to reproduce and predict experimental properties. Previously, a united atom (UA) chain model was developed for the CHARMM27/27r lipids (H{\'e}nin, J., et al. J. Phys. Chem. B. 2008, 112, 7008-7015) but suffers from the flaw that bilayer simulations using the model require an imposed surface area ensemble, which limits its use to pure bilayer systems. A UA-chain model has been developed based on the CHARMM36 (C36) all-atom lipid parameters, termed C36-UA, and agreed well with bulk, lipid membrane, and micelle formation of a surfactant. Molecular dynamics (MD) simulations of alkanes (heptane and pentadecane) were used to test the validity of C36-UA on density, heat of vaporization, and liquid self-diffusion constants. Then, simulations using C36-UA resulted in accurate properties (surface area per lipid, X-ray and neutron form factors, and chain order parameters) of various saturated- and unsaturated-chain bilayers. When mixed with the all-atom cholesterol model and tested with a series of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC)/cholesterol mixtures, the C36-UA model performed well. Simulations of self-assembly of a surfactant (dodecylphosphocholine, DPC) using C36-UA suggest an aggregation number of 53 {\textpm} 11 DPC molecules at 0.45 M of DPC, which agrees well with experimental estimates. Therefore, the C36-UA force field offers a useful alternative to the all-atom C36 lipid force field by requiring less computational cost while still maintaining the same level of accuracy, which may prove useful for large systems with proteins.}, keywords = {analogs /\&/ derivatives/chemistry, chemistry, Cholesterol, Dimyristoylphosphatidylcholine, Lipid Bilayers, Lipids, Micelles, Molecular Dynamics Simulation, Phosphorylcholine, Surface-Active Agents}, doi = {10.1021/jp410344g}, author = {Lee, Sarah and Tran, Alan and Allsopp, Matthew and Lim, Joseph B. and J{\'e}r{\^o}me H{\'e}nin and Klauda, Jeffery B.} } @article {2014|1751, title = {How force unfolding differs from chemical denaturation.}, journal = {Proc. Natl. Acad. Sci. U.s.a}, volume = {111}, year = {2014}, pages = {3413{\textendash}8}, abstract = {

Single-molecule force spectroscopies are remarkable tools for studying protein folding and unfolding, but force unfolding explores protein configurations that are potentially very different from the ones traditionally explored in chemical or thermal denaturation. Understanding these differences is crucial because such configurations serve as starting points of folding studies, and thus can affect both the folding mechanism and the kinetics. Here we provide a detailed comparison of both chemically induced and force-induced unfolded state ensembles of ubiquitin based on extensive, all-atom simulations of the protein either extended by force or denatured by urea. As expected, the respective unfolded states are very different on a macromolecular scale, being fully extended under force with no contacts and partially extended in urea with many nonnative contacts. The amount of residual secondary structure also differs: A significant population of $\alpha$-helices is found in chemically denatured configurations but such helices are absent under force, except at the lowest applied force of 30 pN where short helices form transiently. We see that typical-size helices are unstable above this force, and $\beta$-sheets cannot form. More surprisingly, we observe striking differences in the backbone dihedral angle distributions for the protein unfolded under force and the one unfolded by denaturant. A simple model based on the dialanine peptide is shown to not only provide an explanation for these striking differences but also illustrates how the force dependence of the protein dihedral angle distributions give rise to the worm-like chain behavior of the chain upon force.

}, keywords = {Chemical, Hydrogen-Ion Concentration, Models, Molecular Dynamics Simulation, Protein Conformation, Protein Denaturation, Protein Folding, Protein Unfolding, Ubiquitin, Ubiquitin: chemistry, Urea, Urea: chemistry}, issn = {1091-6490}, url = {http://www.ncbi.nlm.nih.gov/pubmed/24550471}, author = {Guillaume Stirnemann and Kang, Seung-gu and Zhou, Ruhong and Berne, Bruce J} } @article {2014|1964, title = {Interface Matters: The Stiffness Route to Stability of a Thermophilic Tetrameric Malate Dehydrogenase}, journal = {Plos One}, volume = {9}, number = {12}, year = {2014}, month = {dec}, pages = {e113895}, url = {http://dx.doi.org/10.1371\%2Fjournal.pone.0113895}, author = {Kalimeri, Maria and Girard, Eric and Madern, Dominique and Sterpone, Fabio} } @article {2014|1798, title = {The OPEP protein model: from single molecules, amyloid formation, crowding and hydrodynamics to DNA/RNA systems}, journal = {Chem. Soc. Rev.}, volume = {43}, number = {13}, year = {2014}, pages = {4871{\textendash}4893}, doi = {10.1039/c4cs00048j}, author = {F. Sterpone and S. Melchionna and Pierre Tuffery and S. Pasquali and N. Mousseau and T. Cragnolini and Y Chebaro and J.-F. St-Pierre and M. Kalimeri and A. Barducci and Y. Laurin and A. Tek and Marc Baaden and Phuong Hoang Nguyen and Philippe Derreumaux} } @article {2013|1904, title = {Density functional conformational study of 2-O-sulfated 3,6 anhydro-alpha-D-galactose and of neo-kappa- and iota-carrabiose molecules in gas phase and water}, journal = {J. Mol. Model.}, volume = {19}, number = {2}, year = {2013}, month = {feb}, pages = {893{\textendash}904}, doi = {10.1007/s00894-012-1621-y}, author = {Bestaoui-Berrekhchi-Berrahma, Noreya and Philippe Derreumaux and Sekkal-Rahal, Majda and Springborg, Michael and Sayede, Adlane and Yousfi, Noureddine and Kadoun, Abd-Ed-Daim} } @article {2013|1974, title = {{A} gating mechanism of pentameric ligand-gated ion channels}, journal = {Proc. Natl. Acad. Sci. U.s.a.}, volume = {110}, number = {42}, year = {2013}, month = {oct}, pages = {E3987{\textendash}3996}, author = {Calimet, N. and Simoes, M. and Changeux, J. P. and Karplus, M. and Antoine Taly and Cecchini, M.} } @article {2013|1926, title = {How Conformational Flexibility Stabilizes the Hyperthermophilic Elongation Factor G-Domain}, journal = {J. Phys. Chem. B}, volume = {117}, number = {44}, year = {2013}, month = {nov}, pages = {13775{\textendash}13785}, author = {Kalimeri, Maria and Rahaman, Obaidur and Melchionna, Simone and Sterpone, Fabio} } @article {2013|1892, title = {Importance of the Ion-Pair Interactions in the OPEP Coarse-Grained Force Field: Parametrization and Validation}, journal = {J. Chem. Theory Comput.}, volume = {9}, number = {10}, year = {2013}, month = {oct}, pages = {4574{\textendash}4584}, doi = {10.1021/ct4003493}, author = {Sterpone, Fabio and Phuong Hoang Nguyen and Kalimeri, Maria and Philippe Derreumaux} } @inbook {2013|1533, title = {Inquiring Protein Thermostability: Is Resistance to Temperature Stress a Rigidity/Flexibility Trade-off?}, booktitle = {Proceedings of the European Conference on Complex Systems 2012}, year = {2013}, publisher = {Springer International Publishing}, organization = {Springer International Publishing}, author = {Kalimeri, Maria and Melchionna, Simone and Sterpone, Fabio} } @article {2013|1406, title = {{S}tructural basis for ion permeation mechanism in pentameric ligand-gated ion channels}, journal = {Embo J.}, volume = {32}, number = {5}, year = {2013}, month = {mar}, pages = {728{\textendash}741}, author = {Sauguet, L. and Poitevin, F. and Murail, S. and Van Renterghem, C. and Moraga-Cid, G. and Malherbe, L. and Thompson, A. W. and Koehl, P. and Corringer, P. J. and Marc Baaden and Delarue, M.} } @article {2013|1936, title = {Using collective variables to drive molecular dynamics simulations}, journal = {Mol. Phys.}, volume = {111}, number = {22-23}, year = {2013}, pages = {3345{\textendash}3362}, doi = {10.1080/00268976.2013.813594}, author = {Giacomo Fiorin and Michael L Klein and J{\'e}r{\^o}me H{\'e}nin} } @inbook {2012|1575, title = {Advances in Human-Protein Interaction - Interactive And Immersive Molecular Simulations}, year = {2012}, publisher = {Intech, Croatia}, organization = {Intech, Croatia}, chapter = {Protein Interaction / Book 2}, author = {A. Tek and B. Laurent and M. Piuzzi and Z. Lu and Marc Baaden and O. Delalande and Matthieu Chavent and Nicolas F{\'e}rey and C. Martin and L. Piccinali and B. Katz and P. Bourdot and Ludovic Autin}, editor = {W. Cai and H. Hong} } @article {2012|1960, title = {General Anesthetics Predicted to Block the {GLIC} Pore with Micromolar Affinity}, journal = {Plos Comput. Biol.}, volume = {8}, number = {5}, year = {2012}, pages = {e1002532}, publisher = {Public Library of Science}, abstract = {

Author Summary

Although general anesthesia is performed every day on thousands of people, its detailed microscopic mechanisms are not known. What is known is that general anesthetic drugs modulate the activity of ion channels in the central nervous system. These channels are proteins that open in response to binding of neurotransmitter molecules, creating an electric current through the cell membrane and thus propagating nerve impulses between cells. One possible mechanism for ion channel inhibition by anesthetics is that the drugs bind inside the pore of the channels, blocking ion current. Here we investigate such a pore block mechanism by computing the strength of the drugs{\textquoteright} interaction with the pore {\textendash} and hence the likelihood of binding, in the case of GLIC, a bacterial channel protein. The results, obtained from numerical simulations of atomic models of GLIC, indicate that the anesthetics isoflurane and propofol have a tendency to bind in the pore that is strong enough to explain blocking of the channel, even at low concentration of the drugs.

}, doi = {10.1371/journal.pcbi.1002532}, url = {http://dx.doi.org/10.1371\%2Fjournal.pcbi.1002532}, author = {LeBard, David N. and J{\'e}r{\^o}me H{\'e}nin and Roderic G Eckenhoff and Michael L Klein and Brannigan, Grace} } @article {2012|1756, title = {Involvement of the cysteine-rich head domain in activation and desensitization of the P2X1 receptor}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {109}, number = {28}, year = {2012}, pages = {11396{\textendash}11401}, publisher = {National Acad Sciences}, author = {L{\"o}rinczi, {\'E}va and Bhargava, Yogesh and Marino, Stephen F and Antoine Taly and Kaczmarek-H{\'a}jek, Karina and Barrantes-Freer, Alonso and Dutertre, S{\'e}bastien and Grutter, Thomas and Rettinger, J{\"u}rgen and Nicke, Annette} } @article {2011|1473, title = {Coherent vibrational energy transfer along a peptide helix}, journal = {J. Chem. Phys.}, volume = {134}, number = {12}, year = {2011}, month = {mar}, author = {Kobus, Maja and Phuong Hoang Nguyen and Stock, Gerhard} } @article {2011|1665, title = {Community-wide assessment of protein-interface modeling suggests improvements to design methodology.}, journal = {J. Mol. Biol.}, volume = {414}, year = {2011}, month = {nov}, pages = {289{\textendash}302}, abstract = {

The CAPRI (Critical Assessment of Predicted Interactions) and CASP (Critical Assessment of protein Structure Prediction) experiments have demonstrated the power of community-wide tests of methodology in assessing the current state of the art and spurring progress in the very challenging areas of protein docking and structure prediction. We sought to bring the power of community-wide experiments to bear on a very challenging protein design problem that provides a complementary but equally fundamental test of current understanding of protein-binding thermodynamics. We have generated a number of designed protein-protein interfaces with very favorable computed binding energies but which do not appear to be formed in experiments, suggesting that there may be important physical chemistry missing in the energy calculations. A total of 28 research groups took up the challenge of determining what is missing: we provided structures of 87 designed complexes and 120 naturally occurring complexes and asked participants to identify energetic contributions and/or structural features that distinguish between the two sets. The community found that electrostatics and solvation terms partially distinguish the designs from the natural complexes, largely due to the nonpolar character of the designed interactions. Beyond this polarity difference, the community found that the designed binding surfaces were, on average, structurally less embedded in the designed monomers, suggesting that backbone conformational rigidity at the designed surface is important for realization of the designed function. These results can be used to improve computational design strategies, but there is still much to be learned; for example, one designed complex, which does form in experiments, was classified by all metrics as a nonbinder.

}, keywords = {Binding Sites, Models, Molecular, Protein Binding, Proteins}, issn = {1089-8638}, doi = {10.1016/j.jmb.2011.09.031}, author = {Fleishman, Sarel J and Whitehead, Timothy A and Strauch, Eva-Maria and Corn, Jacob E and Qin, Sanbo and Zhou, Huan-Xiang and Mitchell, Julie C and Demerdash, Omar N A and Takeda-Shitaka, Mayuko and Terashi, Genki and Moal, Iain H and Li, Xiaofan and Bates, Paul A and Martin Zacharias and Park, Hahnbeom and Ko, Jun-su and Lee, Hasup and Seok, Chaok and Bourquard, Thomas and Bernauer, Julie and Poupon, Anne and Az{\'e}, J{\'e}r{\^o}me and Soner, Seren and Ovali, Sefik Kerem and Ozbek, Pemra and Tal, Nir Ben and Haliloglu, T{\"u}rkan and Hwang, Howook and Vreven, Thom and Pierce, Brian G and Weng, Zhiping and P{\'e}rez-Cano, Laura and Pons, Carles and Fern{\'a}ndez-Recio, Juan and Jiang, Fan and Yang, Feng and Gong, Xinqi and Cao, Libin and Xu, Xianjin and Liu, Bin and Wang, Panwen and Li, Chunhua and Wang, Cunxin and Charles H. Robert and Guharoy, Mainak and Liu, Shiyong and Huang, Yangyu and Li, Lin and Guo, Dachuan and Chen, Ying and Xiao, Yi and London, Nir and Itzhaki, Zohar and Schueler-Furman, Ora and Inbar, Yuval and Potapov, Vladimir and Cohen, Mati and Schreiber, Gideon and Tsuchiya, Yuko and Kanamori, Eiji and Standley, Daron M and Nakamura, Haruki and Kinoshita, Kengo and Driggers, Camden M and Hall, Robert G and Morgan, Jessica L and Hsu, Victor L and Zhan, Jian and Yang, Yuedong and Zhou, Yaoqi and Kastritis, Panagiotis L and Bonvin, Alexandre M J J and Zhang, Weiyi and Camacho, Carlos J and Kilambi, Krishna P and Sircar, Aroop and Gray, Jeffrey J and Ohue, Masahito and Uchikoga, Nobuyuki and Matsuzaki, Yuri and Ishida, Takashi and Akiyama, Yutaka and Khashan, Raed and Bush, Stephen and Fouches, Denis and Tropsha, Alexander and Esquivel-Rodr{\'\i}guez, Juan and Kihara, Daisuke and Stranges, P Benjamin and Jacak, Ron and Kuhlman, Brian and Huang, Sheng-You and Zou, Xiaoqin and Wodak, Shoshana J and Janin, Jo{\"e}l and Baker, David} } @article {2011|1393, title = {GPU-powered tools boost molecular visualization}, journal = {Briefings Bioinf.}, volume = {12}, year = {2011}, month = {feb}, pages = {689{\textendash}701}, author = {Matthieu Chavent and B. L{\'e}vy and M. Krone and K. Bidmon and J. P. Nomin{\'e} and T. Ertl and Marc Baaden} } @article {2011|1587, title = {Mycoplasma gallisepticum produces a histone-like protein that recognizes base mismatches in DNA}, journal = {Biochemistry}, volume = {50}, year = {2011}, pages = {8692{\textendash}8702}, author = {Dmitri Kamashev and Jacques Oberto and Marina Serebryakova and Alexey Gorbachev and Yulia Zhukova and Sergei Levitskii and Alexey K Mazur and Vadim Govorun} } @article {2011|1474, title = {Simulation of transient infrared spectra of a photoswitchable peptide}, journal = {J. Chem. Phys.}, volume = {135}, number = {12}, year = {2011}, month = {dec}, author = {Kobus, Maja and Lieder, Martin and Phuong Hoang Nguyen and Stock, Gerhard} } @article {2010|1865, title = {An atomistic model for simulations of the general anesthetic isoflurane}, journal = {J. Phys. Chem. B}, volume = {114}, number = {1}, year = {2010}, pages = {604{\textendash}612}, publisher = {Laboratoire d{\textquoteright}Ing{\'e}nierie des Syst{\`e}mes Macromol{\'e}culaires, CNRS, Marseille, France. jhenin@ifr88.cnrs-mrs.fr}, abstract = {An atomistic model of isoflurane is constructed and calibrated to describe its conformational preferences and intermolecular interactions. The model, which is compatible with the CHARMM force field for biomolecules, is based on target quantities including bulk liquid properties, molecular conformations, and local interactions with isolated water molecules. Reference data is obtained from tabulated thermodynamic properties and high-resolution structural information from gas-phase electron diffraction, as well as DFT calculations at the B3LYP level. The model is tested against experimentally known solvation properties in water and oil, and shows quantitative agreement. In particular, isoflurane is faithfully described as lipophilic, yet nonhydrophobic, a combination of properties critical to its pharmacological activity. Intermolecular interactions of the model are further probed through simulations of the binding of isoflurane to a binding site in horse spleen apoferritin (HSAF). The observed binding mode compares well with crystallographic data, and the calculated binding affinities are compatible with experimental results, although both computational and experimental measurements are challenging and provide results with limited precision. The model is expected to be useful for detailed simulations of the elementary molecular processes associated with anesthesia. Full parameters are provided as Supporting Information.}, doi = {10.1021/jp9088035}, author = {J{\'e}r{\^o}me H{\'e}nin and Grace Brannigan and William P Dailey and Roderic G Eckenhoff and Michael L Klein} } @article {2010|1851, title = {Exploring Multidimensional Free Energy Landscapes Using Time-Dependent Biases on Collective Variables}, journal = {J. Chem. Theory Comput.}, volume = {6}, number = {1}, year = {2010}, pages = {35{\textendash}47}, author = {J{\'e}r{\^o}me H{\'e}nin and Giacomo Fiorin and Christophe Chipot and Michael L Klein} } @article {2010|1470, title = {Infrared signatures of the peptide dynamical transition: A molecular dynamics simulation study}, journal = {J. Chem. Phys.}, volume = {133}, number = {3}, year = {2010}, month = {jul}, author = {Kobus, Maja and Phuong Hoang Nguyen and Stock, Gerhard} } @inbook {2010|1569, title = {Molecular dynamics studies of outer membrane proteins : a story of barrels}, year = {2010}, pages = {225{\textendash}247}, publisher = {Royal Society of Chemistry}, organization = {Royal Society of Chemistry}, chapter = {Molecular Simulations and Biomembranes: From Biophysics to Function}, address = {United Kingdom}, author = {S. Khalid and Marc Baaden}, editor = {P.C. Biggin and M.S.P. Sansom} } @article {2010|1971, title = {Multiple binding sites for the general anesthetic isoflurane identified in the nicotinic acetylcholine receptor transmembrane domain.}, journal = {Proc. Natl. Acad. Sci. U.s.a.}, volume = {107}, number = {32}, year = {2010}, pages = {14122{\textendash}14127}, abstract = {An extensive search for isoflurane binding sites in the nicotinic acetylcholine receptor (nAChR) and the proton gated ion channel from Gloebacter violaceus (GLIC) has been carried out based on molecular dynamics (MD) simulations in fully hydrated lipid membrane environments. Isoflurane introduced into the aqueous phase readily partitions into the lipid membrane and the membrane-bound protein. Specifically, isoflurane binds persistently to three classes of sites in the nAChR transmembrane domain: (i) An isoflurane dimer occludes the pore, contacting residues identified by previous mutagenesis studies; analogous behavior is observed in GLIC. (ii) Several nAChR subunit interfaces are also occupied, in a site suggested by photoaffinity labeling and thought to positively modulate the receptor; these sites are not occupied in GLIC. (iii) Isoflurane binds to the subunit centers of both nAChR alpha chains and one of the GLIC chains, in a site that has had little experimental targeting. Interpreted in the context of existing structural and physiological data, the present MD results support a multisite model for the mechanism of receptor-channel modulation by anesthetics.}, doi = {10.1073/pnas.1008534107}, author = {Grace Brannigan and David N LeBard and J{\'e}r{\^o}me H{\'e}nin and Roderic G Eckenhoff and Michael L Klein} } @article {2010|1789, title = {Single-spanning transmembrane domains in cell growth and cell-cell interactions: More than meets the eye?}, journal = {Cell Adh. Migr.}, volume = {4}, number = {2}, year = {2010}, month = {apr}, pages = {313{\textendash}324}, abstract = {

As a whole, integral membrane proteins represent about one third of sequenced genomes, and more than 50\% of currently available drugs target membrane proteins, often cell surface receptors. Some membrane protein classes, with a defined number of transmembrane (TM) helices, are receiving much attention because of their great functional and pharmacological importance, such as G protein-coupled receptors possessing 7 TM segments. Although they represent roughly half of all membrane proteins, bitopic proteins (with only 1 TM helix) have so far been less well characterized. Though they include many essential families of receptors, such as adhesion molecules and receptor tyrosine kinases, many of which are excellent targets for biopharmaceuticals (peptides, antibodies, et al.). A growing body of evidence suggests a major role for interactions between TM domains of these receptors in signaling, through homo and heteromeric associations, conformational changes, assembly of signaling platforms, etc. Significantly, mutations within single domains are frequent in human disease, such as cancer or developmental disorders. This review attempts to give an overview of current knowledge about these interactions, from structural data to therapeutic perspectives, focusing on bitopic proteins involved in cell signaling.

}, keywords = {Animals, Biological, Humans, Membrane Proteins, Models, Protein Structure, Secondary, Signal Transduction, Tertiary}, issn = {1933-6926}, doi = {10.4161/cam.4.2.12430}, author = {Pierre Hubert and Paul Sawma and Jean-Pierre Duneau and Jonathan Khao and J{\'e}r{\^o}me H{\'e}nin and Dominique Bagnard and James Sturgis} } @article {2009|1605, title = {The HSP90 binding mode of a radicicol-like E-oxime determined by docking, binding free energy estimations, and NMR 15 N chemical shifts}, journal = {Biophys. Chem.}, volume = {143}, number = {3}, year = {2009}, pages = {111{\textendash}123}, publisher = {Elsevier}, author = {Spichty, Martin and Antoine Taly and Hagn, Franz and Kessler, Horst and Barluenga, Sofia and Winssinger, Nicolas and Karplus, Martin} } @article {2009|1864, title = {Models for phosphatidylglycerol lipids put to a structural test}, journal = {J. Phys. Chem. B}, volume = {113}, number = {19}, year = {2009}, pages = {6958{\textendash}6963}, publisher = {Center for Molecular Modeling, Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia, Pennsylvania 19104-6323, USA. jhenin@cmm.chem.upenn.edu}, abstract = {Three atomistic empirical models for phosphatidylglycerol (PG) lipids are tested against structural data in the crystal and liquid crystal states. Simulations of the anhydrous crystal of dimyristoyl-phosphatidylglycerol (DMPG) show that only the CHARMM force field describes the conformation and interactions of PG head groups accurately. The other two models do not reproduce the native network of hydrogen bonds, suggesting the presence of biases in their conformational and nonbonded interaction properties. The CHARMM model is further validated in the biologically relevant liquid crystal phase by comparing experimental small-angle X-ray scattering spectra from DMPG unilamellar vesicles with data calculated from fluid bilayer simulations. The good agreement found in this model-free comparison implies that liquid crystal PG bilayers as described by CHARMM exhibit realistic bilayer thickness and lateral packing. Last, this model is used to simulate a fluid bilayer of palmitoyl-oleoyl-phosphatidylglycerol (POPG). The resulting view of the POPG bilayer structure is at variance with that proposed previously based on simulations, in particular, with respect to lateral packing of head groups and the role of counterions.}, keywords = {chemistry, Crystallography, Lipid Bilayers, Models, Molecular, Phosphatidylglycerols, Scattering, Small Angle, Water, X-Ray}, doi = {10.1021/jp900645z}, author = {J{\'e}r{\^o}me H{\'e}nin and Wataru Shinoda and Michael L Klein} } @article {2008|1808, title = {Anomalous diffusion of ions at the surface of hydrated DNA molecule}, journal = {Europhys. Lett.}, volume = {82}, year = {2008}, pages = {46002}, author = {Alla Oleinikova and Ivan Brovchenko and Aliaksei Krukau and Alexey K Mazur} } @article {2008|1970, title = {Embedded cholesterol in the nicotinic acetylcholine receptor}, journal = {Proc. Natl. Acad. Sci. U.s.a.}, volume = {105}, number = {38}, year = {2008}, pages = {14418{\textendash}14423}, publisher = {Center for Molecular Modeling, Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104, USA. grace@cmm.upenn.edu}, abstract = {The nicotinic acetylcholine receptor (nAChR) is a cation-selective channel central to both neuronal and muscular processes and is considered the prototype for ligand-gated ion channels, motivating a structural determination effort that spanned several decades [Unwin N (2005) Refined structure of the nicotinic acetylcholine receptor at 4 A resolution. J Mol Biol 346:967-989]. Purified nAChR must be reconstituted in a mixture containing cholesterol to function. Proposed modes of interaction between cholesterol and the protein range from specific binding to indirect membrane-mediated mechanisms. However, the underlying cause of nAChR sensitivity to cholesterol remains controversial, in part because the vast majority of functional studies were conducted before a medium resolution structure was reported. We show that the nAChR contains internal sites capable of containing cholesterol, whose occupation stabilizes the protein structure. We detect sites at the protein-lipid interface as conventionally predicted from functional data, as well as deeply buried sites that are not usually considered. Molecular dynamics simulations reveal that occupation of both superficial and deeply buried sites most effectively preserves the experimental structure; the structure collapses in the absence of bound cholesterol. In particular, we find that bound cholesterol directly supports contacts between the agonist-binding domain and the pore that are thought to be essential for activation of the receptor. These results likely apply to those other ion channels within the Cys-loop superfamily that depend on cholesterol, such as the GABA receptor.}, doi = {10.1073/pnas.0803029105}, author = {Grace Brannigan and J{\'e}r{\^o}me H{\'e}nin and Richard Law and Roderic G Eckenhoff and Michael L Klein} } @article {2008|1940, title = {HU binds and folds single-stranded DNA}, journal = {Nucl. Acids Res.}, volume = {36}, number = {3}, year = {2008}, pages = {1026{\textendash}1036}, author = {Dmitri Kamashev and Anna Balandina and Alexey K Mazur and Paola B. Arimondo and Josette Rouviere-Yaniv} } @article {2008|1840, title = {Ion dynamics and water percolation effects in DNA polymorphism}, journal = {J. Am. Chem. Soc.}, volume = {130}, number = {1}, year = {2008}, pages = {121{\textendash}131}, author = {Ivan Brovchenko and Aliaksei Krukau and Alla Oleinikova and Alexey K Mazur} } @article {2008|1515, title = {KNOTTIN: the knottin or inhibitor cystine knot scaffold in 2007}, journal = {Nucleic Acids Res.}, volume = {36}, number = {Sp. Iss. SI}, year = {2008}, month = {jan}, pages = {D314-D319}, keywords = {knottin}, author = {Gracy, Jerome and Le-Nguyen, Dung and Gelly, Jean-Christophe and Kaas, Quentin and Heitz, Annie and Chiche, Laurent} } @article {2008|1397, title = {Nonadiabatic vibrational dynamics and spectroscopy of peptides: A quantum-classical description}, journal = {Chem. Phys.}, volume = {347}, number = {1-3}, year = {2008}, month = {may}, pages = {208{\textendash}217}, author = {Kobus, Maja and Gorbunov, Roman D. and Phuong Hoang Nguyen and Stock, Gerhard} } @article {2008|1866, title = {United-Atom Acyl Chains for {CHARMM} Phospholipids}, journal = {J. Phys. Chem. B.}, volume = {112}, number = {23}, year = {2008}, pages = {7008{\textendash}7015}, publisher = {Center for Molecular Modeling, Department of Chemistry, University of Pennsylvania, 231 S. 34th Street, Philadelphia, Pennsylvania 19104-6323, and Research Institute for Computational Sciences, National Institute of Advanced Industrial Science and Technol}, abstract = {In all-atom simulations of lipid membranes, explicit hydrogen atoms contained in the hydrocarbon region are described by a large number of degrees of freedom, although they convey only limited physical information. We propose an implicit-hydrogen model for saturated and monounsaturated acyl chains, aimed at complementing the all-atom CHARMM27 model for phospholipid headgroups. Torsional potentials and nonbonded parameters were fitted to reproduce experimental data and free energy surfaces of all-atom model systems. Comparative simulations of fluid-phase POPC bilayers were performed using the all-hydrogen force field and the present model. The hybrid model accelerates a typical bilayer simulation by about 50\% while sacrificing a minimal amount of detail with respect to the fully atomistic description. In addition, the united-atom description is energetically compatible with all-atom CHARMM models, making it suitable for simulations of complex membrane systems.}, doi = {10.1021/jp800687p}, author = {J{\'e}r{\^o}me H{\'e}nin and Wataru Shinoda and Michael L Klein} } @conference {2007|1517, title = {Atomistic modeling of the membrane-embedded synaptic fusion complex: a grand challenge project on the DEISA HPC infrastructure}, booktitle = {ParCo 2007, Parallel Computing: Architectures, Algorithms and Applications}, volume = {38}, year = {2007}, pages = {729{\textendash}736}, publisher = {John von Neumann Institute for Computing, Juelich, Germany.}, organization = {John von Neumann Institute for Computing, Juelich, Germany.}, url = {http://www.booksonline.iospress.nl/Content/View.aspx?piid=8468}, author = {E. Krieger and L. Leger and M.P. Durrieu and N. Taib and P. Bond and M. Laguerre and R. Lavery and M.S.P. Sansom and Marc Baaden}, editor = {C.B.G.R. Joubert and F. Peters and T. Lippert and M. Buecker and B. Gibbon and and B. Mohr} } @article {2007|2001, title = {{D}ocking of alpha-cobratoxin suggests a basal conformation of the nicotinic receptor}, journal = {Biochem. Biophys. Res. Commun.}, volume = {359}, number = {3}, year = {2007}, month = {aug}, pages = {413{\textendash}418}, publisher = {Academic Press}, author = {Konstantakaki, M. and Jean-Pierre Changeux and Antoine Taly} } @article {2007|1467, title = {Quantum-classical description of the amide I vibrational spectrum of trialanine}, journal = {J. Chem. Phys.}, volume = {126}, number = {5}, year = {2007}, month = {feb}, author = {Gorbunov, Roman D. and Phuong Hoang Nguyen and Kobus, Maja and Stock, Gerhard} } @article {2007|1861, title = {Water clustering and percolation in low hydration DNA shells}, journal = {J. Phys. Chem. B}, volume = {111}, number = {12}, year = {2007}, pages = {3258{\textendash}3266}, author = {Ivan Brovchenko and Aliaksei Krukau and Alla Oleinikova and Alexey K Mazur} } @article {2006|1754, title = {{I}mplications of the quaternary twist allosteric model for the physiology and pathology of nicotinic acetylcholine receptors}, journal = {Proc. Natl. Acad. Sci. U.s.a.}, volume = {103}, number = {45}, year = {2006}, month = {nov}, pages = {16965{\textendash}16970}, author = {Antoine Taly and Corringer, P. J. and Grutter, T. and Prado de Carvalho, L. and Karplus, M. and Jean-Pierre Changeux} } @article {2006|1757, title = {Implications of the quaternary twist allosteric model for the physiology and pathology of nicotinic acetylcholine receptors}, journal = {Proceedings of the National Academy of Sciences}, volume = {103}, number = {45}, year = {2006}, pages = {16965{\textendash}16970}, publisher = {National Acad Sciences}, author = {Antoine Taly and Corringer, Pierre-Jean and Grutter, Thomas and De Carvalho, Lia Prado and Karplus, Martin and Jean-Pierre Changeux} } @article {2006|1842, title = {Structural changes of region 1-16 of the Alzheimer disease amyloid beta-peptide upon zinc binding and in vitro aging}, journal = {J. Biol. Chem.}, volume = {281}, number = {4}, year = {2006}, pages = {2151{\textendash}2161}, author = {Severine Zirah and Sergey A. Kozin and Alexey K Mazur and Alain Blond and Michel Cheminant and Isabelle Segalas-Milazzo and Pascale Debey and Sylvie Rebuffat} } @article {2006|1948, title = {Water percolation governs polymorphic transitions and conductivity of DNA}, journal = {Phys. Rev. Lett.}, volume = {97}, number = {13}, year = {2006}, pages = {137801}, author = {Ivan Brovchenko and Aliaksei Krukau and Alla Oleinikova and Alexey K Mazur} } @conference {2006|1421, title = {Yeast Naked DNA Spatial Organization Predisposes to Transcriptional Regulation}, booktitle = {International Conference on Computational Science and its Applications (ICCSA 2006)}, volume = {3984}, year = {2006}, month = {may}, pages = {222{\textendash}231}, address = {Glasgow, United Kingdom}, author = {O. Matte-Tailliez and J .H{\'e}risson and Nicolas F{\'e}rey and O. Magneau and P.-E. Gros and F. K{\'e}p{\`e}s and R. Gherbi} } @article {2004|1513, title = {The KNOTTIN website and database: a new information system dedicated to the knottin scaffold}, journal = {Nucleic Acids Res.}, volume = {32}, number = {Sp. Iss. SI}, year = {2004}, month = {jan}, pages = {D156-D159}, author = {Gelly, JC and Gracy, J and Kaas, Q and Le-Nguyen, D and Heitz, A and Chiche, L} } @article {2004|1801, title = {Molecular cloning of a mollusk glucanase}, journal = {Comp. Biochem. Physiol.}, volume = {137}, number = {2}, year = {2004}, pages = {169{\textendash}178}, author = {Valeri B. Kozhemyako and Denis V. Rebrikov and Sergey A. Lukyanov and Ekaterina A. Bogdanova and Antoine Marin and Alexey K Mazur and Svetlana N. Kovalchuk and Elena V. Agafonova and Victoria V. Sova and Ludmila A. Elyakova and Valeri A. Rasskazov} } @article {2004|1778, title = {Single-stranded breaks relax intrinsic curvature in {DNA}?}, journal = {Biochemistry}, volume = {43}, number = {25}, year = {2004}, pages = {8160{\textendash}8168}, author = {Dimitri E. Kamashev and Alexey K Mazur} } @article {2002|1946, title = {Comparative bending dynamics in DNA with and without regularly repeated adenine tracts}, journal = {Phys. Rev. E}, volume = {66}, number = {1}, year = {2002}, pages = {011917}, author = {Alexey K Mazur and Dimitri E. Kamashev} } @article {2001|1841, title = {Sheep prion protein synthetic peptide spanning helix 1 and beta-strand 2 (residues 142-166) shows beta-hairpin structure in solution}, journal = {J. Biol. Chem.}, volume = {276}, number = {49}, year = {2001}, pages = {46364{\textendash}46370}, author = {S. A. Kozin and G. Bertho and Alexey K Mazur and H. Rabesona and J. P. Girault and T. Haertle and M. Takahashi and P. Debey and G. H. Hoa} } @article {1992|1697, title = {Schematic methods for probabilistic enzyme kinetics}, journal = {J. Theor. Biol.}, volume = {155}, year = {1992}, pages = {387{\textendash}407}, author = {Alexey K Mazur and A. V. Kuchinski} } @article {1991|1593, title = {A combined study of aggregation, membrane affinity and pore activity of natural and modified melittin}, journal = {Biochim. Biophys. Acta}, volume = {1069}, number = {1}, year = {1991}, month = {oct}, pages = {77{\textendash}86}, author = {Stankowski, S and Pawlak, M and Kaisheva, E and Charles H. Robert and Schwarz, G} } @article {1991|1767, title = {Mechanism of the rearrangement of the bicyclo [4.2. 0] octan system to the bicyclo [3.2. 1] octan system}, journal = {Tetrahedron}, volume = {47}, year = {1991}, pages = {229{\textendash}238}, abstract = {

A concerted mechanism has been demonstrated for the rearrangement of a tetracyclic ion including a bicyclo [4.2.0] octan system to hibaol, using a selective deuteration on the migrating bond. The stereochemistry of the selectively introduced deuterium was determined by three routes: 1. comparison of the high field 1H NMR spectra of the deuterated and undeuterated compounds, using double irradiation; 2. high field 1H NMR, coupled with molecular mechanics calculations; 3. two dimensional homo and heteronuclear NMR.

}, doi = {10.1016/S0040-4020(01)80919-4}, url = {http://www.sciencedirect.com/science/article/pii/S0040402001809194}, author = {Bastard, Josette and Do Khac, Duc and Fetizon, Marcel and Chantal Pr{\'e}vost and Beloeil, Jean-Claude} } @article {1986|1595, title = {A study of interaction of an O-specific polysaccharide from Pseudomonas fluorescense with antibodies}, journal = {Bioorg. Chem.}, volume = {12}, year = {1986}, pages = {265{\textendash}272}, author = {T. F. Solovjeva and G. A. Naberezhnykh and Alexey K Mazur and V. A. Khomenko and Yu. S. Ovodov} }